ID 111327
Author
Keywords
Salivary gland
autoimmunity
RbAp48
Sjögren’s syndrome
Content Type
Journal Article
Description
Recent evidences suggest that the apoptotic pathway plays a central role in tolerazing T cells to tissue-specific self antigen, and may drive the autoimmune phenomenon in the salivary glands. We found that retinoblastoma-associated protein RbAp48 overexpression induces p53-mediated apoptosis in the salivary glands caused by estrogen deficiency. We demonstrated that transgenic (Tg) expression of RbAp48 resulted in the development of autoimmune exocrinopathy resembling Sjögren’s syndrome (SS). CD4+T cell-mediated autoimmune lesions in the salivary glands were aggravated with age, in association with autoantibody productions. We obtained evidences that salivary epithelial cells can produce interferon-γ(IFN-γ) besides interleukin (IL)-18, which activates interferon regulatory factor-1 (IRF-1), and class II transactivator (CIITA). Indeed, the autoimmune lesions into Rag2-/- mice were induced by the adoptive transfer of lymph node cells from RbAp48-Tg mice. These results indicate a novel immunocompetent role of epithelial cells that can produce IFN-γ, resulting in loss of local tolerance prior to developing gender-based autoimmunity. The studies reviewed the molecular mechanisms on the development of salivary gland autoimmunity, and gender-related differences in SS.
Journal Title
The Journal of Medical Investigation
ISSN
13496867
13431420
NCID
AA11166929
AA12022913
Publisher
Faculty of Medicine Tokushima University
Volume
56
Issue
Supplement
Start Page
185
End Page
191
Sort Key
185
Published Date
2009-12
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Oral Sciences